Clinical trials are often conducted to allow safety and efficacy data to be collected for new drugs or devices. Clinical trials can take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and approval is granted in the country where the trial is taking place. Depending on the type of product and the stage of its development, investigators enroll healthy volunteers and/or patients into small pilot studies initially, followed by larger scale studies in patients that often compare the new product with the currently prescribed treatment. As positive safety and efficacy data are gathered, the number of patients is typically increased. Clinical trials may vary in size from a single center in one country to multicenter trials in multiple countries. Although a sizable cost for a full series of clinical trials may be incurred, the burden of paying for all the necessary people and services is typically borne by the sponsor who may be a governmental organization, a pharmaceutical, or biotechnology company. Since the diversity of roles may exceed resources of the sponsor, often a clinical trial is managed by an outsourced partner such as a contract research organization.
Clinical trials involving new drugs are commonly classified into four phases with pharmaceutical studies. However, pre-clinical studies are often conducted in order to obtain preliminary efficacy, toxicity, and pharmacokinetic information before the clinical trials themselves. Pre-clinical studies assist pharmaceutical companies to decide whether a drug candidate has scientific merit for further development as an investigational new drug.
Phase I trials is the first stage of testing in human subjects. A small (20-50) group of healthy volunteers is typically selected. This phase includes trials designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These trials are often conducted in an inpatient clinic, where the subject can be observed by full-time staff.
Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered not to work as planned or to have toxic effects.
Phase III studies are randomized controlled multicenter trials on large patient groups (300-3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is in comparison with current gold standard treatment. Because of the size and comparatively long duration, Phase III trials are typically the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions. It is common practice that certain Phase III trials will continue while the regulatory submission is pending at the appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Once a drug has proved satisfactory after Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life. This collection of information makes up the regulatory submission that is provided for review to the appropriate regulatory authorities in different countries. Regulatory authorities review the submission to determine whether to give the sponsor approval to market the drug. Most drugs undergoing Phase III clinical trials in the United States may be marketed under Federal Drug Administration (FDA) norms with proper recommendations and guidelines, but in case of any adverse effects being reported anywhere, the drugs may be recalled immediately from the market. While most pharmaceutical companies refrain from this practice, many drugs undergo Phase III clinical trials in the market.
Phase IV trial is also known as the post marketing surveillance trial. Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold. Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive (finding a new market for the drug) or other reasons (e.g., the drug may not have been tested for interactions with other drugs, or on certain population groups such as pregnant women, who are unlikely to subject themselves to trials). The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials.
Each phase of the drug approval process is typically treated as a separate clinical trial. The drug-development process normally proceeds through all four phases over many years. If the drug successfully passes through Phases I, II, and III, the drug will usually be approved by the national regulatory authority for use in the general population. Phase IV involves post-approval studies. A clinical trial typically takes a number of years to complete. For example, about eight years passes from the time a cancer drug enters clinical trials until it receives approval from regulatory agencies for sale to the public. Drugs for other diseases often have similar timelines. Consequently, avoiding delays in collecting data during the clinical trial may reduce development costs while providing beneficial drugs to the public in a more expeditious manner.